The present invention relates to novel polymorphs of efavirenz, processes for their preparation and pharmaceutical compositions containing them.
Pharmaceutical products with HIV reverse transcriptase (including its resistant varieties) inhibitors are described in U.S. Pat. No. 5,519,021. An especially important compound among those disclosed is efavirenz, (4S)-6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one. Efavirenz has the following structural formula:

This compound is used for the preparation of a medicament having nonnucleoside HIV-1 reverse transcriptase inhibiting activity that is useful in the prevention or treatment of infection by HIV and the treatment of AIDS. Efavirenz is sold commercially as SUSTIVA® by Bristol Myers Squibb.
WO patent application publication No. 98/33782 disclosed three crystalline forms, Form I (characterized by an x-ray powder diffraction patterns having peaks expressed as 2θ at 6.1, 6.4, 10.4, 10.9, 12.3, 13.2, 14.2, 15.2, 16.9, 18.4, 19.2, 20.1, 21.2, 22.3, 23.0, 24.9, 25.9, 26.3, 27.2, 28.1, 28.6, 29.1, 29.5, 30.7, 32.4 and 38.3 degrees), Form II (characterized by an x-ray powder diffraction patterns having peaks expressed as 2θ at 3.6, 6.3, 11.1, 12.8, 13.3, 14.3, 16.1, 16.9, 18.5, 19.2, 19.6, 20.6, 21.3, 22.6, 23.2, 24.4, 24.9, 26.0, 26.8, 27.6, 28.4, 29.2, 29.6, 30.6, 31.9 and 33.8 degrees) and Form III (characterized by an x-ray powder diffraction patterns having peaks expressed as 2θ at 7.2, 10.9, 13.7, 14.5, 16.7, 19.1, 19.6, 20.8, 21.7, 22.3, 22.8, 23.2, 23.9, 24.5, 24.9, 25.8, 27.0, 27.6, 29.3, 30.3, 30.7, 31.3, 33.4, 38.4 and 39.2 degrees) of efavirenz.
WO patent application publication No. 99/64405 disclosed five crystalline forms, Form 1 (characterized by an x-ray powder diffraction patterns having peaks expressed as 2θ at about 6.0, 6.3, 10.3, 10.8, 14.1, 16.8, 20.0, 20.5, 21.1 and 24.8 degrees), Form 2 (characterized by an x-ray powder diffraction patterns having peaks expressed as 2θ at about 6.8, 9.2, 12.3, 16.2, 21.4, 22.7, 24.1 and 28.0 degrees), Form 3 (characterized by an x-ray powder diffraction patterns having peaks expressed as 2θ at about 7.1, 7.3, 11.0, 13.8, 20.9, 23.3, 27.9 and 33.5 degrees), Form 4 (characterized by an x-ray powder diffraction patterns having peaks expressed as 2θ at about 3.6, 6.3, 9.7, 11.0, 12.7, 13.2, 16.1, 19.2, 19.5, 20.6 and 24.3 degrees) and Form 5 (characterized by an x-ray powder diffraction patterns having peaks expressed as 2θ at about 10.2, 11.4, 11.6, 12.6, 19.1, 20.6, 21.3, 22.8, 24.8, 27.4, 28.2 and 31.6 degrees) of efavirenz.
We have discovered a stable novel crystalline form of efavirenz. The novel form is at least as stable as the reported forms (Form I, Form II, Form III, Form 1, Form 2, Form 3, Form 4 and Form 5). The novel crystalline form is stable over the time and has good flow properties and so, the novel crystalline form is suitable for formulating efavirenz.
Amorphous form of efavirenz has not been reported in the prior art. So, there is a need for stable amorphous form of efavirenz for better pharmaceutical preparations.
One object of the present invention is to provide a stable novel crystalline form of efavirenz, process for preparing it and a pharmaceutical composition containing it.
Another object of the present invention is to provide a novel stable amorphous form of efavirenz, process for preparing it and a pharmaceutical composition containing it.